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Angew Chem Int Ed Engl. 2017 Oct 9;56(42):13036-13040. doi: 10.1002/anie.201707536. Epub 2017 Sep 11.

Neutralization of Pathogenic Fungi with Small-Molecule Immunotherapeutics.

Author information

1
Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT, 06511, USA.
2
Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
3
Prokaryotics, Inc., 1000 Morris Ave, STEM Bldg., Suite 5-13, Union, NJ, 07083, USA.

Abstract

Systemic fungal infections represent an important public health concern, and new antifungal agents are highly desirable. Herein, we describe the design, synthesis, and biological evaluation of a novel class of antifungal compounds called antibody-recruiting molecules targeting fungi (ARM-Fs). Our approach relies on the use of non-peptidic small molecules, which selectively bind fungal cells and recruit endogenous antibodies to their surfaces, resulting in immune-mediated clearance. Using the opportunistic fungal pathogen Candida albicans as a model, we identified a highly specific bifunctional molecule able to mediate the engulfment and phagocytosis of C. albicans cells by human immune cells in biologically relevant functional assays. This work represents a novel therapeutic approach to treating fungal illness with significant potential to complement and/or combine with existing treatment strategies.

KEYWORDS:

antibodies; antifungal agents; cell recognition; drug discovery; immunology

PMID:
28793176
DOI:
10.1002/anie.201707536
[Indexed for MEDLINE]

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